Figure 5.

A. Schizophrenia risk genes are enriched for genes that harbor rare LoF variation in neurodevelopmental disorders, such as ASD and DD. OR, odds ratio; rare LoF, genes that harbor rare loss-of-function variation in each disorder; constrained; LoF-intolerant genes that harbor rare variation in each disorder. B. Psychiatric disorders display widespread pleiotropy that the same set of genes can be impacted in multiple psychiatric disorders. This widespread pleiotropy can be partly explained by the mode of genetic variation: e.g. schizophrenia risk genes impacted by common variation may also cause neurodevelopmental disorders when impacted by LoF rare variation. However, cautions need to be exercised as this does not necessarily suggest that schizophrenia is simply a less severe form of neurodevelopmental disorders. Instead, this result suggests that identifying the mode of variation (common vs. rare, non-coding vs. protein-disrupting) is as important as variation discovery to allow comprehensive understanding of pleiotropy among psychiatric disorders.